All publications herein are incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. The following description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.
Myocardial infarction (MI) or acute myocardial infarction (AMI), commonly known as a heart attack is the interruption of blood supply to a part of the heart, causing heart cells to die. Myocardial infarction is caused by ischaemic or ischemic heart disease (IHD), or myocardial ischaemia, which is characterized by reduced blood supply due to a partial or complete blockage of an artery that carries blood to the heart, usually due to coronary artery disease (atherosclerosis of the coronary arteries). The decrease in blood flow reduces the heart's oxygen supply. Myocardial ischemia is an imbalance between myocardial oxygen supply and demand. Its risk increases with, for example, age, smoking, hypercholesterolaemia (high cholesterol levels), diabetes, and hypertension (high blood pressure), and is more common in men and those who have close relatives with ischaemic heart disease. Myocardial ischemia is the pathological state underlying ischaemic heart disease.
In the event of a myocardial infarction, maximizing myocardial salvage from regions of pronounced ischemia in patients suffering an infarction is the most important goal of any therapeutic strategy delivered to the patient. The therapeutic standard for countering the acute ischemic burden is the re-establishment of blood flow, while reducing ischemia-reperfusion injury, via percutaneous transluminal coronary angioplasty (PTCA), coronary artery bypass grafting (CABG) or fibrinolysis. Of these two approaches, the most sought after therapeutic regiment is PTCA. Reperfusion therapies do not always re-establish flow and can lead to microvascular obstructions (MVOs). It has been shown that MVOs occur at the site of severe ischemic injury and that they have been associated with poor prognosis and reduced survival rates in the months and years post reperfusion. It is also known that MVOs are associated with larger infarcts and that larger infarcts lead to poorer remodeling in the chronic stage of disease culminating in heart failure. Since heart failure is a growing epidemic in the Western World, and most heart failures have origins in ischemic heart disease it is desirable to reduce ischemia-reperfusion injury in right at the acute setting.
Reperfusion can cause further damage and cell death, resulting in ischemia/reperfusion injury (IRI). There are no established drugs to prevent or treat IRI. A major cause of myocardial damage/death from IRI is a superoxide burst at reperfusion. Given the problems associated with existing reperfusion therapies, such as microvascular obstructions, there is a need in the art for reperfusion therapies that restore blood flow to the ischemic regions of the heart without any injuries to said region.